Stem cells are cells that are capable of self-renewal and of giving rise to more differentiated cells. Embryonic stem (ES) cells can differentiate into the multiple specialized cell types that collectively comprise the body. In addition to being of immense scientific interest, the property of pluripotency gives human ES cells great clinical promise for applications in regenerative medicine such as cell/tissue replacement therapies for disease.
Several different methods are currently used to obtain ES cells. In one method, an ES cell line is derived from the inner cell mass of a normal embryo in the blastocyst stage (See U.S. Pat. Nos. 5,843,780 and 6,200,806, Thompson, J. A. et al. Science, 282:1145-7, 1998). A second method for creating pluripotent ES cells utilizes somatic cell nuclear transfer (SCNT). In this technique, the nucleus is removed from a normal egg, thus removing the genetic material. The nucleus of a donor diploid somatic cell is introduced directly into the enucleated oocyte, e.g., by micromanipulation, or the donor diploid somatic cell is placed next to the enucleated egg and the two cells are fused. The resulting cell has the potential to develop into an early embryo from which the portion containing the stem cell producing inner cell mass can be obtained. In a third method, the nucleus of a human cell is transplanted into an enucleated animal oocyte of a species different from the donor cell. See, e.g., U.S. Pat. Pub. No. 20010012513. The resultant chimeric cells are used for the production of pluripotent ES cells, in particular human-like pluripotent ES cells. Disadvantages of this technique are that these chimeric cells may contain unknown viruses and retain the mitochondria of the animal species.
The traditional ES cell isolation methods suffer from several limitations when applied to generating human ES cells. These include ethical controversies associated with the source of the cells as well as technical challenges. A significant limitation to the productive utilization of ES cells for clinical applications is the difficulty associated with generating ES cells that are genetically matched to individual patients. There exists a significant need for alternative methods of generating pluripotent cells.